The specialized functions of blood platelets are primarily concerned with hemostasis and thrombosis. In these functions the plasma membrane plays a central role. Since many of these reactions involve proteins on the platelet membrane's surface, it becomes essential to better understand the components involved and their mechanisms of interaction. Accordingly, the proposed research is designed to answer the following questions: (1) What is the primary site of thrombin action on the membrane surface? Experiments are described to determine if hydrolysis of glycoprotein II is sufficient for thrombin induced reactions to the platelet. (2) What are the effects of aggregating agents on the surface structure of the human platelet plasma membrane? Preliminary results have shown that the lactoperoxidase iodination probe, which was developed in this laboratory, can detect thrombin induced alterations in the molecular organization of the platelet membrane. The proposed research will compare the thrombin induced alterations with those that may be induced by other agents that induce platelets to aggregate in order to determine what structural alterations are important to the aggregation process. (3) Which membrane components are actually involved in the aggregation process? To establish which membrane components are involved in the aggregation process, the interaction of isolated surface proteins with intact platelets will be examined. BIBLIOGRAPHIC REFERENCES: Jenkins, C.S.P., Phillips, D. R., Clemetson, K.J., Meyer, D., Larrieu, M.-J. and Luscher, E.F. Platelet membrane glycoprotein implicated in ristocetin-induced aggregation. Studies of the proteins on platelets from patients with Bernard-Soulier syndrome and von Willebrand's disease. J. Clin. Invest. 57, 112-124 (1976). Phillips, D.R. and Agin, P.P. Thrombin interaction with human platelets. Evidence for both a binding and a proteolytic site on the plasma membrane. In Platelets: Recent Advances in Basic Research and Clinical Aspects (Proceedings of the International Symposium on Blood Platelets, 1974, Istanbul, Turkey), Ulutin, O.N., Ed., International Congress Series 357 (1975).